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在cDC1中SLC38A2和谷氨酸信号决定了抗瘤免疫力

Chuansheng Guo¹, Zhiyuan You¹, Hao Shi¹

¹Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.

|July 5, 2023

概括

谷氨酸作为代谢检查点,控制瘤细胞和树突细胞 (DC) 之间的通信. 通过改善DC功能和克服治疗耐药性,补充谷氨酸可以增强抗瘤免疫力.

科学领域:

免疫学
代谢途径
癌症研究

背景情况:

瘤细胞逃避免疫反应,部分原因是瘤与免疫相互作用的不充分理解.
树突细胞 (DCs),特别是cDC1s,对于启动抗瘤T细胞反应至关重要.
营养素在适应性免疫和DC功能中的作用在很大程度上仍未定义.

研究的目的:

研究营养素,特别是谷氨酸在调节DC功能和抗瘤免疫力中的作用.
阐明谷氨酸如何影响瘤细胞和cDC1之间的交声.
探索谷氨酸补充剂作为一种治疗策略,

主要方法:

营养素查和整合性分析,以确定影响DC功能的关键营养素.
在瘤细胞和cDC1中通过SLC38A2转运器研究谷氨酸的吸收.
在DC中分析涉及FLCN和TFEB的谷氨酸信号通路.

主要成果:

谷氨酸作为细胞间代谢检查点,决定瘤-cDC1交叉声和增强cDC1介导的T细胞激活.
内胺补充剂抑制瘤生长并克服对免疫疗法的抵抗性.
瘤细胞和cDC1s争夺谷氨酸;谷氨酸是促进cDC1功能的主要氨基酸.
通过FLCN传递谷氨酸信号会影响TFEB功能,而在DC中缺乏FLCN会损害cDC1功能.

结论:

瘤细胞和cDC1s之间的谷氨酸介导的代谢交叉对瘤免疫逃避至关重要.
在cDC1中胺的获取和信号是DC激活的限制因素.
向cDC1中的谷氨酸代谢是一种增强抗瘤免疫力的潜在治疗策略.

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